Microvasculatures in the sub-dermal layer, if accessed, provide vital information about the health of the measured individual. For example, blood-glucose level, oxygen content, hormonal concentration, etc., can be directly measured from blood properties. Often to achieve this information, the skin must be penetrated by a needle in order to draw the blood into a sampling device. Use of such a needle is typically associated with pain, exposure of the blood to the environment, or risk of infection due to the rupture of the skin. A less invasive alternative to this procedure is to have a sensor embedded within the sub-dermal layer. Again, this procedure (depending on the scale) to achieve the implant is problematic both due to the process of placing the implant and the potential rejection by the patient's body.
Another area relevant to the subject matter of the present invention is in angioplasty procedures. Percutaneous transluminal angioplasty (PTA) and percutaneous transluminal coronary angioplasty (PTCA) are established, proven methods for re-opening stenotic or occluded arteries in a minimally invasive way. A balloon is placed in the stenotic segment of the artery using a catheter and then expanded until the lumen reaches its desired diameter. The use of an expanded balloon to forcibly open the narrowed section of the artery requires very high pressure (15 bars) and tends to cause injury to the vessel walls. The body's natural response to such injury is hyperproliferation, an abnormally high rate of cell division, which results in lumen narrowing and thus decreased function of the vessel. This is counterproductive to the initial goal of opening the stenotic or occluded artery.
To counter the hyperproliferation response of the vessel, an antiproliferative taxane drug such as paclitaxel may be used. A single, short contact of tissue with a small dose of paclitaxel has been shown to inhibit local cell proliferation. Paclitaxel is a mitotic inhibitor often used in cancer chemotherapy because cancerous cells exhibit hyperproliferation. Paclitaxel was originally derived from the bark of Pacific yew trees, but is now produced from other bioengineering methods. The mechanism of action of paclitaxel is the stabilization of microtubules through binding to tubulin, thus interfering with their normal breakdown during cell division. This has the net effect of reduced cell division rates, and counteracts hyperproliferation.
Antiproliferative taxanes have important properties for minimizing the hyperproliferation response of damaged vessel walls. They have high lipophilicity (hydrophobicity) and bind tightly to various cell constituents, giving good local retention at the delivery site. Though hydrophilic compounds penetrate easily into tissues, they also clear quickly. Paclitaxel is a hydrophobic compound and diffuses into the arterial wall from the lumen where it is delivered (See Literature Reference No. 1).
A typical procedure for treating a stenotic or occluded artery is to use a paclitaxel-coated angioplasty balloon, with the paclitaxel serving its purpose of inhibiting hyperproliferation following the balloon opening process. The major limitations on this process are the following:
1. The need of long inflation time in order to make sure the paclitaxel diffusion to the arterial wall is sufficient, which may cause excessive arterial wall injury. Previous study shows that 40-60 minutes are required to transfer roughly 90% of the initial dose of paclitaxel to the arterial wall (See Literature Reference No. 1);
2. In order to obtain the optimum benefit of hyperproliferation inhibition, it is important that the paclitaxel coating is not lost or washed off by the blood stream while advancing into the stenotic segment of the artery. Previous study shows that the rate of paclitaxel being washed away from the uninflated balloon by the blood stream is up to 1.2% from the initial dose per minute (See Literature Reference No. 2);
3. Potential loss of paclitaxel coating due to contact with the healthy arterial wall while advancing into the stenotic segment of the artery; and
4. The maximum dose of paclitaxel that can be applied on a single balloon is around 11 mg (10 μg/mm2), which is significantly less than the paclitaxel dose approved by the FDA for Taxol (See Literature Reference No. 1).
It should be noted that the use of carbon nanotubes for the purpose of reinforcing the material properties of a balloon catheter has been suggested in U.S. Pat. No. 7,037,562. However, in that patent, the carbon nanotubes were mixed with the base material for the purpose of strengthening the material and not for drug delivery purposes. In addition, the carbon nanotubes were not aligned or partially anchored in the base material in a way such that they would protrude from the surface and facilitate drug delivery, rendering the device non-functional for that purpose.
Thus, a continuing need exists for a minimally invasive blood monitoring device which protects the extracted fluid from the atmosphere, and also for a drug delivery system which can effectively deliver high amounts of a desired drug to an affected site in a relatively short time period with minimal drug loss to passing body fluids.
The following references are cited throughout this application. For clarity and convenience, the references are listed herein as a central resource for the reader. The following references are hereby incorporated by reference as though fully included herein. The references are cited in the application by referring to the corresponding literature reference number.
(1) Creel, C. J., M.A. Lovich, and E. R. Edelman, Arterial paclitaxel distribution and deposition. Circulation Research, 2000. 86(8): p. 879-884.
(2) Scheller, B., U. Speck, C. Abramjuk, U. Bernhardt, M. Bohm, and G. Nickenig, Paclitaxel balloon coating, a novel method for prevention and therapy of restenosis. Circulation, 2004. 110(7): p. 810-814.
(3) Bronikowski, M. J., Longer nanotubes at lower temperatures: The influence of effective activation energies on carbon nanotube growth by thermal chemical vapor deposition. Journal of Physical Chemistry C, 2007. 111(48): p. 17705-17712.